T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies

Xue, Yang; Tai, Yuki; Yamamoto, Hiromi; Mori, Daiki; Sakai, Kaori; Miyazaki, Takuya; Owa, Mikito; Kometani, Kohei; Ebina, Isao; Omiya, Ryusuke; Hattori, Kunihiro; Inoue, Takeshi; Ise, Wataru; Shinnakasu, Ryo; Kurosaki, Tomohiro

doi:https://doi.org/10.1093/intimm/dxag003

T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies

Xue, Yang; Tai, Yuki; Yamamoto, Hiromi et al.

International Immunology, 2026, 38(6), 383-395

Number of Access:11（2026-07-22 14:09 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/105210

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Title	T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies
Creator	CreatorName Xue, Yang
	NRID 1000060985000 1000060985000 ORCID 0009-0007-7554-8512 0009-0007-7554-8512 researchmap permalink ytai ytai CreatorName Tai, Yuki
	CreatorName Yamamoto, Hiromi
	CreatorName Mori, Daiki
	CreatorName Sakai, Kaori
	CreatorName Miyazaki, Takuya
	CreatorName Owa, Mikito
	NRID 1000050437258 1000050437258 CreatorName Kometani, Kohei
	CreatorName Ebina, Isao
	CreatorName Omiya, Ryusuke
	Scopus Author ID 35596425700 35596425700 CreatorName Hattori, Kunihiro
	CreatorName Inoue, Takeshi
	NRID 1000070323483 1000070323483 researchmap permalink wataruise wataruise Scopus Author ID 6602103314 6602103314 CreatorName Ise, Wataru
	NRID 1000000451758 1000000451758 CreatorName Shinnakasu, Ryo
	NRID 1000050178125 1000050178125 ORCID 0000-0002-6352-304X 0000-0002-6352-304X researchmap permalink kurosakitomohiro kurosakitomohiro Scopus Author ID 7102059533 7102059533 CreatorName Kurosaki, Tomohiro
Subject	antibody maturation
Subject	follicular helper T cells
Description	This is a pre-copyedited, author-produced version of an article accepted for publication in International Immunology following peer review. The version of record Xue Y., Tai Y., Yamamoto H., et al. T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies. International Immunology 38, 383 (2026) is available online at: https://doi.org/10.1093/intimm/dxag003.
Abstract	The development of vaccines eliciting broadly neutralizing influenza antibodies (bnAbs) is an extraordinary challenge. One hypothetical proposal is that CD4+ T-cell help to rare immuno-subdominant bnAb class memory B cells is one critical factor to cause these B cells to re-enter secondary germinal centers (GCs) and generate potent bnAbs. In this regard, we previously showed that the prototypic hemagglutinin stem vaccine does not contain the dominant CD4+ T-cell epitope. Here, to test the above hypothesis, we examined the effects of adding a single influenza T-cell epitope to the stem vaccine in an influenza pre-infected booster mouse model. We found that this fused booster vaccine efficiently recruited antistem memory B cells with prior GC experience into the secondary GCs in draining lymph nodes. Furthermore, these secondary GC-experienced cells evolved, thereby contributing to generation of more potent neutralizing activity toward variant viruses. Thus, our results suggest the importance of T-cell help in generating potent bnAbs by recruiting rare subdominant memory B cells into secondary GCs, and have implications for vaccine design.
Publisher	Oxford University Press
Source Title	International Immunology
Volume (Issue)	38(6)
Page	383-395
Date of Issued	2026-01-16
Language	English
Handle URL	https://hdl.handle.net/11094/105210
PISSN	09538178
eISSN	14602377
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1093/intimm/dxag003
Access Rights	embargoed access
CopyRight	The full-text file will be made open to the public on 16 January 2027 in accordance with the publisher's policy.
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	International Immunology. 2026, 38(6), p. 383-395
DC.title	T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies
DC.creator	Xue, Yang
	Tai, Yuki
	Yamamoto, Hiromi
	Mori, Daiki
	Sakai, Kaori
	Miyazaki, Takuya
	Owa, Mikito
	Kometani, Kohei
	Ebina, Isao
	Omiya, Ryusuke
	Hattori, Kunihiro
	Inoue, Takeshi
	Ise, Wataru
	Shinnakasu, Ryo
	Kurosaki, Tomohiro
DC.publisher	Oxford University Press
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2026-01-16
DC.identifier	https://doi.org/10.1093/intimm/dxag003
DC.subject	antibody maturation
DC.subject	follicular helper T cells
DC.description	This is a pre-copyedited, author-produced version of an article accepted for publication in International Immunology following peer review. The version of record Xue Y., Tai Y., Yamamoto H., et al. T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies. International Immunology 38, 383 (2026) is available online at: https://doi.org/10.1093/intimm/dxag003.
DCTERMS.abstract	The development of vaccines eliciting broadly neutralizing influenza antibodies (bnAbs) is an extraordinary challenge. One hypothetical proposal is that CD4+ T-cell help to rare immuno-subdominant bnAb class memory B cells is one critical factor to cause these B cells to re-enter secondary germinal centers (GCs) and generate potent bnAbs. In this regard, we previously showed that the prototypic hemagglutinin stem vaccine does not contain the dominant CD4+ T-cell epitope. Here, to test the above hypothesis, we examined the effects of adding a single influenza T-cell epitope to the stem vaccine in an influenza pre-infected booster mouse model. We found that this fused booster vaccine efficiently recruited antistem memory B cells with prior GC experience into the secondary GCs in draining lymph nodes. Furthermore, these secondary GC-experienced cells evolved, thereby contributing to generation of more potent neutralizing activity toward variant viruses. Thus, our results suggest the importance of T-cell help in generating potent bnAbs by recruiting rare subdominant memory B cells into secondary GCs, and have implications for vaccine design.
DC.rights	The full-text file will be made open to the public on 16 January 2027 in accordance with the publisher's policy.
DC.format	105210
citation_title	T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies
citation_author	Xue, Yang
	Tai, Yuki
	Yamamoto, Hiromi
	Mori, Daiki
	Sakai, Kaori
	Miyazaki, Takuya
	Owa, Mikito
	Kometani, Kohei
	Ebina, Isao
	Omiya, Ryusuke
	Hattori, Kunihiro
	Inoue, Takeshi
	Ise, Wataru
	Shinnakasu, Ryo
	Kurosaki, Tomohiro
citation_publisher	Oxford University Press
citation_language	English
citation_date	2026-01-16
citation_journal_title	International Immunology
citation_volume	38
citation_issue	6
citation_firstpage	383
citation_lastpage	395
citation_doi	https://doi.org/10.1093/intimm/dxag003
citation_public_url	https://hdl.handle.net/11094/105210

T-cell help is a limiting factor for rare anti-influenza memory B cells to re-enter germinal centers and generate potent broadly neutralizing antibodies

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